Holán V, Zajícová A, Krulová M, Plsková J, Fric J, Filipec M
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Faculty of Natural Sciences, Charles University, Prague, Department of Ophthalmology, Charles University, Prague, Czech Republic.
Immunology. 2000 Nov;101(3):404-11. doi: 10.1046/j.1365-2567.2000.00111.x.
Oral administration of antigen has been shown to be effective for both positive and negative modulation of immune responses. In the present study we characterized changes in the reactivity of the immune system after oral immunization with allogeneic spleen cells. Mice were orally immunized for 10 consecutive days with fresh allogeneic spleen cells, and the phenotype, proliferative response, cytotoxic activity and cytokine production profile of recipient spleen cells were assessed 1 or 7 days after the last immunization dose. Although no significant changes in the proportion of CD4+, CD8+ or CD25+ cells were observed in the spleen of orally immunized mice, significant activation of alloreactivity in spleen cells was found. Cells from orally immunized mice exhibited enhanced proliferation and cytotoxic activity after stimulation with specific allogeneic cells in vitro, and produced considerably higher concentrations of interferon-gamma (IFN-gamma) and significantly less interleukin (IL)-4 than did cells from control mice. The production of IL-2 was essentially unchanged and that of IL-10 was only slightly increased. The systemic allosensitization induced by oral immunization was demonstrated in vivo by increased resistance to the growth of allogeneic tumours induced by subcutaneous inoculation of high doses of tumour cells. In addition, orthotopic corneal allografts in orally immunized recipients were rejected more rapidly (in a second-set manner) than in control, untreated recipients. These data show that oral immunization with allogeneic cells modulates individual components of the immune response and that specific transplantation immunity, rather than tolerance, is induced in the treated recipients.
口服抗原已被证明对免疫反应的正向和负向调节均有效。在本研究中，我们对用同种异体脾细胞进行口服免疫后免疫系统反应性的变化进行了表征。小鼠连续10天口服新鲜的同种异体脾细胞，在最后一次免疫剂量后1天或7天评估受体脾细胞的表型、增殖反应、细胞毒性活性和细胞因子产生谱。尽管在口服免疫小鼠的脾脏中未观察到CD4 +、CD8 +或CD25 +细胞比例的显著变化，但发现脾细胞中的同种异体反应性有显著激活。口服免疫小鼠的细胞在体外受到特异性同种异体细胞刺激后表现出增强的增殖和细胞毒性活性，并且产生的干扰素-γ（IFN-γ）浓度明显高于对照小鼠，而白细胞介素（IL）-4的产生则明显减少。IL-2的产生基本未变，IL-10的产生仅略有增加。通过对皮下接种高剂量肿瘤细胞诱导的同种异体肿瘤生长的抵抗力增加，在体内证明了口服免疫诱导的全身同种异体致敏。此外，口服免疫受体中的原位角膜同种异体移植比未治疗的对照受体更快地（以二次反应的方式）被排斥。这些数据表明，用同种异体细胞进行口服免疫可调节免疫反应的各个组成部分，并且在接受治疗的受体中诱导的是特异性移植免疫而非耐受性。
